Macrolides

Question 1

MOA

Answer 1

Bacteriostatic

Inhibit protein synthesis by reversibly binding to the 50s ribosomal subunit
induce dissociation of peptidyl transfer RNA from the ribosome during the elongation phase

Question 2

Marcolide drugs

Answer 2

Erythromycin
Azithromycin
Clarithromycin

Question 3

Mechanism or resistance

Answer 3

1. Active efflux - mef gene - low level resistance to macrolides
2. Altered binding site - erm gene which methylates the macrolide binding site - high level resistance to all macrolides, clindamycin and synercid
3. Cross resistance occurs between all macrolides

Question 4

Spectrum of activity
Gram positive aerobes

Answer 4

C>E>A
PSSP
MSSA

Question 5

Spectrum of activity
Gram negative aerobes

Answer 5

A>C>E
H. Influenzae (not erythromycin)
Moraxella
Neisseria spp.

Question 6

Spectrum of activity
Anaerobes

Answer 6

Upper airway anaerobes

Question 7

Spectrum of activity
Atypical bacteria

Answer 7

Legionella Pneumophila
Mycobacterium avium Complex

Question 8

Absorption

Answer 8

Erythromycin - Variable absorption - food may decrease absorption

Clarithromycin - acid stable and well absorbed regardless of presence of food

Azithromycin - acid stable regardless of presence of food, low serum concentration

Question 9

Distribution

Answer 9

Minimal CSF penetration
Extensive tissue and cellular distribution
Very large Vds

Question 10

Elimination

Answer 10

Erythromycin is excreted in bile and metabolized by Cyp450

Clarithromycin is metabolized by kidney and required dose adjustment when CrCl <30

Azithromycin is eliminated by biliary excretion

Variable half lives NOTE 68 hours for azithro

None of the macrolides are removed during hemodialysis

Question 11

Clinical use

Answer 11

Respiratory tract infection

Community acquired pneumonia - atypical coverage

STDs: single 1gram dose of azithro

MAC: Azithro for prophylaxis and Clarithro for treatment

Alternative for penicillin allergic patients

Question 12

Adverse effects

Answer 12

Thrombophlebitis - IV erythro and azithro (Dilution of dose, slow administration, large vein)

QTC prolongation

Gastrointestinal - N/V, Diarrhea, Dyspepsia (can take with food to help)

Question 13

Drug interactions
Erythromycin and clarithromycin (ONLY)

Answer 13

Erythro and Clarithro are inhibitors of Cytocrhrom p450 and can increase concentrations of the following drugs:

Theophylline, Carbamazepine, Cyclosporine, Phenytoin, Warfarin, Digoxin, Valproci acid

Question 14

Which of the following antibiotics is least likely to interact with warfarin?

A. Azithromycin
B. Levofloxacin
C. Ciprofloxacin
D. Clarithromycin
E. Moxifloxacin

Answer 14

A. Azithromycin - It can interact and should be monitored but least likely to do so

Question 15

Which of the following antibiotics does NOT have activity against atypical bacteria (e.g., Legionella pneumophila)?
A. Azithromycin
B. Levofloxacin
C. Amoxicillin-clavulanate
D. Clarithromycin
E. Moxifloxacin

Answer 15

C Amoxicillin- clavulanate

Question 16

Azithromycin Drug interaction

Answer 16

Interacts with Mg and Aluminum containing antacids

INTERACTION WITH CALCIUM IS CLINICALLY insignificance so does not matter